Transcutaneous PO2 and cardiovascular observations in the sheep fetus following the reduction of uterine blood flow

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Künzel et al., Observations following reduction of uterine blood flow 85

J. Perinat. Med.

8(1980)85

Transcutaneous P(>2 and cardiovascular observations in the sheep fetus following the reduction of uterine blood flow

Wolfgang Künzel, Eckart Kastendieck, Carl-Sylvius Kurz, Rene Paulik

Department of Obstetrics and Gynecology University Würzburg, Germany

The transcutaneous P02 (tcPO2)-electrode has been widely used in the intensive neonatal care and has been proved to be a valuable method for the indirect continuous recording of the arterial P02 [4]. Recently it was also applied to monitor the P02 of the fetus during labor [4]. Information concerning the comparison of the tcP02 and the P02 in the fetal aorta and carotid artery and its alteration during fetal hypoxia are still lacking.

The relationship of the cardiovascular response of the fetus and the tcP02 to fetal hypoxia has not been examined, too. It was therefore important to investigate the changes of the tcP02 and the fetal cardiovascular parameters simultaneously. For this purpose a sheep preparation was used to study the response of the tcP02-electrode, the P02 in the fetal aorta and fetal heart rate to acute alterations of uterine blood flow. It could be shown that the tcP02 responded with a delay to the alterations of the arterial P02. In addition it could be shown that the tcP02 was influenced by a peripheral vasoconstriction that topk place äs a response to fetal hypoxia.

l Material and methods

The experiments were performed on 11 near term pregnant sheep (fetal weight: ränge 1800-4800 g, mean 3390 g (SD 1120 g). Prior to Operation the sheep was kept in a seperate room for 24 hours where it had free access to water.

1.1 Anaesthesia

Pentobarbital was given intravenously followed by a single injection of Alloferin® (RÖCHE) (Alcu- roniumchlorid) for relaxation. The ewe was then intubated and mechanically ventilated by an ENGSTROM respirator which maintained a positiv endexspiratory pressure Ventilation and so preven- ting pulmonary atelectasis. Anaesthesia was maintained with 0.5% halothane in 30% oxygen balan- ced with nitrogen oxide. The maternal femoral artery was exposed and a catheter with an inflatable balloon advanced into the maternal aorta (Fogarty 30 F).

l .2 Preparation and Instrumentation of the ani- mal

The uterine hörn was delivered by a midline ab- dominal incision and opened in an avascular area.

The fetal leg was then delivered and the left femoral artery was isolated. Two catheters were advanced into fetal aorta, one for blood sampling, the other for the continuous measurement of fetal arterial blood pressure (FA BP) and fetal heart rate (FHR). Over the right femoral artery a fiber glass optic system was introduced into the fetal aorta. It served for the continuous measurement of the oxygen Saturation (Hämoreflektometer, ScHWARZER-Corporation, Germany). The System was calibrated by the blood samples at control and at zero. After shaving the fetal head the precali- 0300-5577/80/0008-0085$02.00

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brated tcP02 electrode (HELLIGE. Germany) was glued to thehairfree area with Histoacryl® (BRAUN / Melsungen).

In four additional experiments the fetal carotid artery was isolated. A T-tube was inserted so that a free flow was guaranteed. Blood samples could be drawn at the same time from the aorta and the carotid artery while the tcP02 was measured.

Uterine blood flow was reduced for three minutes to zero by an inflatable balloon which was located about 10 cm above the bifurcation of the aorta.

The complete reduction of flow could be as- sured by the blood pressure which was measured in the aorta below the occlusion and in four experiments by measuring uterine blood flow of the right and left uterine artery, respectively, with an electromagnetic flow probe (STATHAM-Cor-

x<poration).

REDUCTION of

UTERINE BUOOD FLOW

t c P

2 Results

2.1 The transcutaneous PO2, the arterial P02 in the aorta (PO2^) and the oxygen Saturation (SO2ja) determined continuously and by sampling

Fig. 1. shows the course of the tcPO2, the arterial PO2 and the oxygen Saturation in the aorta äs a response to the reduction of uterine blood flow.

It is apparent that the fall of the SO2 measured by blood sampling and by direct continuous recording shows a good correlation. The S02 at control was 53.4% (SD 13.4) (N = 13) and feil within 2 to 3 minutes to 5.6% (SD 3.1) and 4.1% (SD 1.9), respectively.

The tcP02 and the P02,a indicate at control a difference of about 4-5 mmHg. Following the reduction of uterine blood flow the tcPO2 responded after 26.6 (SD 7.9) sec, whereas the S02 feil after 12.3 (SD 3.1) sec. The P02>a approached zero after 2 min (0.9 mmHg (SD 2.0)) whereas the tcPO2 was zero after 3 min (0.4 mmHg (SD 0.7)).

After the occlusion of the maternal aorta was- released and uterine blood flow increased, the SO2

rose after 23.9 (SD 14.4) sec. The rise of the tcPO2

after the release of UBF was extremely delayed and occurred after 72.6 (SD 41.9) sec.

02(o)

02 .aorta

OXYGEN SATURATION continuous (o)

Fig. 1. The course of the transcutaneous PO2 (tcPO2), the PO2 in the blood sample from the fetal aorta (upper part of the fig.), the continuously measured oxygen saturation in the fetal aorta and in the sample (lower part of the fig.) before, during and following the complete reduction of uterine blood flow. (Number of öbservations: 13;

mean ± Standard deviation). Note the difference between the tcPO2 and the PO2 in the fetal aorta, the delayed response of the electrode to hypoxia and during recovery.

2.2 The cardiovascular response of the fetus to the reduction of uterine blood flow

The fetal cardiovascular response to the reduction of UBF is shown in Fig. 2. The systolic blood pressure (BP) and the diastolic BP were at control 62 (SD 10) mmHg and 43 (SD 7) mmHg, respectively. Fetal heart rate (FHR) was 175 (SD 28) beats per minute. Following the reduction of uterine blood flow (UBF) the BP started to rise after 23.2 (SD 8.2) sec accompanied by an increase of the puls pressure after 31.5 (SD 10.2) sec and fetal heart rate feil after 31.3 (SD 17.3) sec. Three minutes after UBF had been completely reduced fetal heart rate was 81 (SD 30) b/min and the BP 81 (SD 22) mmHg and 51 (SD 17) mmHg, respectively. With the release of UBF FHR showed

J.Perinat. Med.8(1980)

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Künzel et al., Observations following reduction of uterine blood flow 87

(mmHg) 120·

100-

80·

60

20

Systolic and Diastolic Blood Pressure

REDUCTION

of MEAN * SD

(permin) Fetal Heart Rate 200-

160-

120-

80-

MEAN* SD

0 2 ' l ' 6 8 1 0 1 2 ' U ' time (min)' p

Fig. 2. Systolic and diastolic blood pressure and fetal heart rate äs a response to the complete reduction of uterine blood flow. (Number of observations: 13; mean

± Standard deviation). Fetal heart rate feil and the blood pressure rose at a response to the re<}uction of uterine blood flow. During recovery the increase of fetal heart rate was related to the decline of the systolic and diastolic blood pressure.

an immediate rise which was accompanied by an increase of the systolic and diastolic BP. During the further course the BP feil again accompanied by a normalisätion of the FHR. The previous control values were achieved 7—8 min after UBF was released.

2.3 Analyas and discussion of the tcPO2 measurements

Concerning the tcP0² readings three facts became apparent.

J. Perinat. Med. 8(1980)

a. The delay of the tcP02-response compared to changes of the arterial P02.

b. the delay of the tcP02-response after fetal hypoxia during the recovery period

and

c. the difference that exists between the tcP02 and the PO2 in the fetal aorta.

2.4 To a. The delay of the tcP02 to fetal hypoxia The reduction of uterine blood flow (UBF) to zero Interrupts the transfer of oxygen from the mother to the fetus so that the oxygen requirement of the fetus has to be covered by the oxygen which is stored in the fetal blood and in the maternal placental blood. If the oxygen consumption of the fetus remains constant a continuous fall of the P02 and S02 should occur. Compared to the continuously measured S0² in the fetal aorta the tcPO2 feil with a delay of about 15 sec. Provided that the cutaneous blood flow is not altered during the initial 20 sec following the reduction of UBF the delay may be caused by the response time of the electrode itself and by the equilibration time between the fetal tissue and the arterialized cutaneous blood.

2.5 To b. The delay of the tcPO² after fetal hypoxia during the recovery period

The cause of the delayed response of the tcPO² after fetal hypoxic episodes is clearly indicated by the additional experiments in Fig. 3. Uterine blood flow was reduced for 2 min to zero. Fetal blood pressure rose and fetal heart rate feil äs a response to the declining PO². A normalization of the arterial PO2 took place within 2 to 3 min after the reduction of flow was released. The tcP0² however reached the ränge of the control 5 min late.

It is well known that during hypoxia catecholamines are released [2] and that this may account for a vasoconstriction that takes place in the peripheral circulation. The reduced blood flow under the tcPO²-electrode may then be responsible for the delayed tcPO² normalization after hypoxic episodes.

To prove the influence of the catecholamines on the tcP0² Norepinephrine wasgiven intravenously

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BLOOD PRESSURE (mmHg)

120-

80-

40-

o o EWE No. 5-78 No.6-76 SYSTOUC BP

DIASTOLIC BP Reduction of Uterine Blood Flow

2 4l l6

time (min)—

Fig. 3. Systolic and diastolic blood pressure, fetal heart rate and the transcutaneous PO2 (tcPO2) a^d the PO2 in the carotid artery äs a response to the reduction of uterine blood flow for 2 min in ewe Nr. 5/78 and ewe Nr. 6/78. Note, that after uterine blood flow was restored, the FHR is still low, whereas the PO2>a *s i*1 *he normal ränge. The tcPO2 recovers simultaneously with the normalization of the blood pressure and FHR.

tcP02

(mmHg) 30-i

25-

20- 15-

10-

EWE No. 5-78 Norepinephr ine 0.01 mg/kg

>P30"

"XX

90" 60"

10l

T

₂₅

5 10 15 20 25 30 P02 ( o Aorta ; · A. carotis ) (mmHg)

Fig. 4. The transcutaneous PO2 versus the PO2 in the fetal aorta (open circles) and in the carotid artery (closed circles), respectively, following a Norepinephrine-injection (0.01 mg/kg). The numbers indicate the time in sec and min following the injection. As a response to the injection of NE into the fetal vena cava the tcP02 feil without äny significant change of the arterial PO2 during the initial 60 sec. During the further course the PO2 in the aorta and carotid artery feil, whereas the tcPO2 rose. This effect was induced by the reduction of uterine blood flow which was simultaneously measured and by the release of the vasoconstriction under the electrode. With in- creasing utrine blood flow after 5 min the tcPO2 and the PO2 in the artery rose.

The dotted line is the line of identity.

Despite of the fäll of the arterial PO^? the tcPO² rose again and the arterial PO² was 5 min after injection equal with the tcP0². During the further sequence the tcPO² äs well äs the arterial PO² rose again caused by a nonnalization of uterine blood flow.

into the fetus. In Fig. 4 the response of the PO² in the carotid artery and in the aorta was compared with the tcPO².

0.01 mg/kg Norepinephrine given intravenously was followed by a fall of the tcPO² without äny significant alterations of the arterial PO² during the initial 60 sec. The delayed fall of the arterial P0² was due to a reduction of uterine blood flow.

2.6 ToC.ThetcPO²-arterialPO²difference It is well known for a long time that the carotid arterial blood contains more oxygen than does that in the descending aorta of the fetus (reviewed by DAWES 1968 [3]). This difference may account for the observed tcPO²—PO²^-difference in the sheep fetus. In four preparations in addition a T-tube was inserted into the left carotid artery so J.Perinat.Med. 8 (1980)

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Künzel et al., Observations following reduction of uterine blood flow 89 tcPQ2

(mm Hg) 30-,

20-

10-

,'<-O Line of Identity

l ' l ^ l 10 20 30 Aorta; g£ A.carotis UmmHg)

Fig. 5. The correlation of the tcPO2 and the PO2 in the aorta (open Symbols) and in the carotid artery (closed Symbols). Each symbol represents one animal. The broken line is the line of identity. There exists a very good correlation between the tcPO2 an^ the arterial PO² (aorta and carotid artery), respectively, in the PO² ränge of 10-30 mmHg.

The calculated regression lines are:

tcP02 = 2.04 + 0.87 · P02 a carotis, (r= 0.923;N = 21,2

< 0.001); tcP02 = 5.22 + 0.81 - PO2 aorta, (r = 0.8972;

N = 21,2 < 0.001).

that free passage of blood to the brain was guaranteed. Blood was sampled from the carotid artery and the descending aorta simultaneously while the tcPO2 was measured. In Fig. 5 the tcPO2

is plotted against the P02 in the carotid artery. It is obvious tixat the tcPO2 is very close correlated to the P02 in the aorta by äbout 2 mmHg and that may be the reason for the observed tcP02—P02>a- difference.

3 General discussion

For fetal surveillance each tool is appreciated that delivers more Information concerning the fetal

J.Perinat.Med. 8 (1980)

condition during labor äs at the present state available. The tcP02-electrode, applied by HUCH and others (reviewed by HUCH et al., 1977 [4]) to the fetus during parturition seems to give such additional Information.

That the P02 of the fetus falls during labor es- pecially during the second stage is known since it was possible to analyze the blood from the fetal scalp [1,6,7]. The tcP02 recording has however evidenced that during contraction the P02 falls.

In this context two questions should be discussed more extensively:

a. Which additional Information do we have in hand by recording the tcP02 compared to fetal heart rate

b. Which errors may be created by concluding from the tcP02 reading to the pathomechanism of fetal heart rate deceleration.

Toa.:

Uterine blood flow is reduced during each uterine contraction and parallel to the reduced blood supply to the Uterus the fetal PO2 falls.

In Fig. l it is demonstrated that the reduction of flow is followed by the decline of the arterial P0² and tcP02. Heart rate feil and blood pressure rose simultaneously indicating the reduced fetal 02

supply. Despite the delayed response of the tcP02

the fall of fetal heart rate reflected the fall of the P02 in the fetal circulation.

Even during recovery the increase of the heart rate was related to the rise of the oxygen Saturation.

After the reduction of flow was released, the S02

started to rise after 23.9 (SD 14.4) sec and heart rate after 31.6 (SD 17.3) sec. The increase of the tcPO² was however extremely delayed: 72.6 (SD 41.9) sec. If the course of the tcPO² however is compared with the course of the blood pressure it can be seen that the tcPO2 is reflected by the blood pressure and similar to the fetal heart rate.

That seems to prove that at normal "central"

arterial oxygenation the peripheral circulation is still reduced and this may be also valid for other organs. So far, the tcPO2 measurement shows very clearly that the delayed recovery of the fetal heart rate is related to the extreme secretion of catecholamines during hypoxia resulting in peripheral vasoconstriction and elevated blood pressure.

Despite the restored central oxygenation it may be

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suggested that fetal heart rate, fetal blood pressure and also tcPO2 come back to control values if the response of the catecholamines in the peripheral circulation disappears. The additional Information we obtain by tcP02 monitoring will be to get an insight into the fetal peripheral circulation which allows us to appreciate the stress condition of the fetus.

Tob.:

The fall of fetal heart rate äs a response to acute hypoxia is closely related to the decline of the oxygen in the fetal blood and bound to a critical fall of the SO2. In this context the time at which the SO2 falls is dependent on the fetal oxygenation before hypoxia was induced and on the oxygen consumption of the fetus [5]. These parameters interfere with the delayed response time of the N electrode.

In addition during the recovery time the increase of the heart rate is paralleled by the rise of the

arterial P02. At this time the tcPO2 is still low because it Starts to rise # the vasoconstriction in the peripheral circulation changes. From this point it may be misleading to conclude from the peri- pheral oxygenation that heart rate alteration are not related to fetal oxygenation.

In summa ry, the tcPO2 electrode applied to the fetal head is reflecting the PO2 of the carotid artery. Under hypoxic conditions, however, the tcPO2-PO2>a-difference rises indicating the re- duced blood flow and the poor oxygenation in the cutaneous tissue and probably of other Organs.

Fetal heart rate reflects the changes of the tcP02. This may be also valid for the human fetus. More simultaneous measurements of the tcP02 and FHR in the human are, however, necessary to find out if the tcPO2 offers additional Information and whether the tcPO2-monitoring is a valueable tool for fetal surveillance during labor.

Summary

On 11 near term pregnant sheep the response of the fetal transcutaneous oxygen partial pressure (tcPO2) was compared with the alteration of the oxygen Saturation (SC>2) and the PO2 in the fetal aorta (FA), fetal heart rate (FHR) and fetal arterial blood pressure (FA BP) following the reduction of uterine blood flow (UBF).

The FA SO2 changed 12.3 (SD 3.1) sec and the tcPO2

26.6 (SD 7.9) sec after UBF was reduced. The tcPO2

response was also delayed after UBF was restored: 72.6 (SD 41.9) sec compared to the SO2 response: 23.9 (SD 14.4) sec. The reduction of UBF was paralleled by a rise of the FA BP and a fall of FHR. They were at control within 10 min after the reduction of UBF was released reflecting the normaiization of the tcPO2.

There was a tcPO2-FA PO2-difference which was due to the difference that exist betwecn the carotid artery PO2 and the PO2 in the fetal aorta.

The delayed response of the tcPO2 electrode was due to the response time of the electrode itself. The delay during the recovery period however was predominantly due to the peripheral vasoconstriction äs proved by Nor- epinephrine injection. The tcPO2 reflects very close the fall of the FA BP and the rise of the FHR during the recovery period and vice versa. The importance of the tcPO2-PO2,a difference for the fetal condition during labor has still to be worked out.

Keywords: Cardiovascular System, fetal heart rate, fetal shock, transcutaneous-arterial PO2 difference, transcutaneous P02.

Zusammenfassung

Transcutaner PO2 und kardiovaskuläre Beobachtungen am Schaf-Feten bei Reduktion der uterinen Durchblutung Bei 11 trächtigen Schafen wurde am Ende der Tragzeit der fetale transcutane Sauerstoffpartialdruck (tcPO2) gemessen und die Änderung des tcPO2 auf die Reduktion der uterinen Durchblutung mit dem Abfall der Sauerstoff- sättigung (SO2) und dem PO2 in der fetalen Aorta (FA), der fetalen Herzfrequenz (FHR) und der Reaktion des fetalen Blutdrucks verglichen.

Durch vollständige Drosselung der uterinen Durchblutung fiel die FASO2 in 12,3 (SD 3,1) sec. ab. Der tcPO2 zeigte einen Abfall nach 26,6 (SD 7,9) sec. Nach dem Anstieg der Uterusdurchblutung war die Normalisierung des tcPO2 ebenfalls gegenüber dem FA SO2 verzögert: Nach Freigabe der Durchblutungsdrosselung stieg der tcPO2

nach 72,6 (SD 41,9) sec. an, während der Anstieg der Sauerstoffsättigung bereits nach 23,9 (SD 14,4) sec.

erfolgte.

J. Perinat. Med. 8 (1980)

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Künzel et al., Observations following reduction of uterine blood flow 91

Die Reduktion der uterinen Durchblutung verursachte einen Anstieg des fetalen Blutdrucks und einen Abfall der fetalen Herzfrequenz. 10 Min. nach Normalisierung der uterinen Durchblutung hatten Blutdruck und Herz- frequenz den Ausgangswert annähernd wieder erreicht.

Die Normalisierung des Blutdrucks reflektierte die Normalisierung des tcPO2 ·

Es bestand eine tcPO2-FA PO2-Differenz, deren Ursache in der Differenz des PO2 zwischen der Arteria carotis und der Aorta bestand.

Die verzögerte Reaktionszeit des tcP0² zu Beginn der Durchblutungsreduktion ist bedingt durch die Reak- tionszeit der Elektrode, während die verzögerte Nor- malisierung des tcPO² nach der Hypoxie in erster Linie durch periphere Vasokonstriktion hervorge- rufen wurde. Dies konnte durch Injektion von Nor- epinephrin nachgewiesen werden.

Der Verlauf der tcPO² gibt daher einen Einblick in die kardiovaskuläre Reaktion des Feten. Es gilt daher zu prüfen, welche Bedeutung die transkutan-arterielle PO2- Differenz für Zustand der Feten während der Geburt hat.

Schlüsselwörter: Fetale Herzfrequenz, fetaler Schock, kardiovaskuläres System, transkutan-arterielle PO²-Differenz, transkutaner PO2.

Resume

Po2 transcutanee et observations cardio-vasculaires chez le foetus de mouton a la suite de la reduction du flux sanguin uterin.

La pression partielle transcutanee d'oxygene (tcPO²) a ete mesuree chez 11 moutons gravides en fin de grossesse et les variations de la tcPO2 consecutives a la reduction de Tirrigation uterine ont ete mises en correlation avec la chute de la Saturation d'oxygene (SO²) et la PO² dans l'aorte foetale (AF), ainsi qu'avec la frequence cardiaque foetale (FCF) et la reaction de la tension arterielle foetale.

Sous Teffet de l'abolilion de l'irrigation uterine, la AF SO2

chuta en l'espace de 12,3 sec. (SD 3,1). La chute de la tcPO2 se produisait apres 26,6 sec. (SD 7,9). Apres retablissement de Firrigation uterine la normalisation de la tcPO² etait egalement decalee par rapport a la AF SO²: apres liberation de Pirrigation uterine la tcPO² s'elevait apres 72,6 sec. (SD 41,9) alors que l'augmentation de la Saturation d'oxygene se produisait deja apres 23,9 sec.

(SD 14,4).

La reduction de l'irrigation uterine avaitpourconsequence une elevation de la tension sanguine foetale et une chute de la frequence cardiaque foetale. 10 minutes apres lai normalisation de l'irrigation uterine la tension sanguine et la frequence cardiaque avaient retrouvre leurs valeurs de depart. La normalisation de la tension sanguine re- fletaitcelledelatcPO2.

L'on notait une difference entre la tcPO2 et la AF PO2, dont la causc residait en la difference de PO2 entre Tariere carotide et l'aorte.

La reaction retardee de la tcPO2 au debut de la reduction de l'irrigation est liee au temps de latence de l'electrode, alors que la normalisation retardee de la tcPO2 apres ITiypoxie est liee avnt tout a la vasoconstriction peri- pherique. Ceci a pu etre prouve par l'administration de norepinephrine.

L'evolution de la tcPO2 permet ainsi une approche de la reaction cardio-vasculaire du foetus. II s'agit donc de determiner l'importance de la difference de PO2 transcutaneo-arterielle sur Status foetal.

Mots-cles: Difference transcutaneo-arterielle de PO², frequence cardiaque foetale, PO² transcutanee, schock foetal, Systeme cardiovasculaire.

Acknowledgement: This work was supported by the Deutsche Forschungsgemeinschaft (Ku 341-5) and the Dr. ROBERT PFLEGER Stiftung, Bamberg.

Presented in part on the First International Symposium of Continuous Transcutaneous Blood Gas Monitoring, Marburg 1978.

Bibliography

[1] BERG, D., J. HÜTER, G. KÖHNLEIN, F. KUBLI:

Die Mikroblutuntersuchung am Fetus. Arch. Gynäk.

203(1966)287

[2]CQMLINE, R. S., M. SlLVER: Development of activity in the adrenal medulla of the fetus and new- born aniinal. Brit. Med. Bull. 22 (1966) 16

J. Perinat. Med. 8 (1980)

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[3] DAWES, G. S.: The foetal circulation. In: DAWES, G. S. (ed.): Fetal and neonatal physiology. Year Book Medical Publishers, Chicago-London 1968 [4] HUCH, A., R. HUCH, H. SCHNEIDER, G. ROOTH:

Continuous tianscutaneous monitoring of fetal oxygen tension during labor. Brit. J. Obstet. Gynaec. 84 (1977) l

[5] KÜNZEL, W., E. KASTENDIECK, C. S. KURZ:

Heart rate and blood pressure response of the sheep fetus foilowing the reduction of uterine blood flow.

26th Annual Meeting of the Society for Gynecologic Investigation, San Diego 1979

[6] SALING, E.: Neues Vorgehen zur Untersuchung des Kindes unter der Geburt. Arch. Gynäk. 197 (1962) [7] WULF, K. H., W. KÜNZEL, V. LEHMANN: Ver-108 gleichende Untersuchungen der aktuellen Blutgase und des Säure-Base-Status im fetalen und maternen Kapillarblut während der Geburt. Z. Geburtsh.

Gynäk. 167(1967)113

Received April 27, 1979. Accepted August 23, 1979.

Prof. Dr. W. Künzel Department of Gynecology University of Würzbuig Josef-Schneider-Str. 4 D-8700 Würzburg West-Germany

J. Perinat. Med. 8 (1980)